Patent GB-1435384-A (GB)
Title: Psychopharmacologically active peptides
IPC: C07K1/113
Filed: 1973-05-15
Abstract: 1435384 Peptides AKZO NV 15 May 1973 [24 May 1972] 22984/73 Heading C3H [Also in Division C2] Peptides of the general formula A-Glu(Q)- His-X, wherein either Glu(Q) or His is present in the D-form and A is H-L-Met, H-L-Met(# O), H-L-Met(#O 2 ), desamino-Met, desamino- Met(#O), desamino-Met(#O 2 ) or in which B is a C 1-6  alkylene group, Q is -OH or -NH 2  and X is -OH, a phenylalkylamino group of the formula in which R 1  is H, halogen, OH or C 1-4  alkyl or alkoxy and Alk is C 1-6  alkylene, or -L-Phe-Y, in which Y is -OH, -NH-Alk-NR 2 R 3 , in which Alk is C 2-6  alkylene, R 2  is H or C 1-4  alkyl and R 3  is H, C 1-4  alkyl or amidino, -L-Lys-Z, -D-Lys-Z, -L-Arg-Z or -D-Arg-Z, in which Z is -OH, an N-(#-indolyl-C 1-6  alkyl)amino group, a phenylalkylamino group of the above formula, L-Trp-OH, L-Trp-Gly-OH, -L-Phe-OH or LPhe-Gly-OH, and functional derivatives thereof are prepared by conventional methods. Intermediates which are prepared are Z-DGlu(OtBu) - His - OMe, H - D - Glu(OtBu)- His - OMe.2HCl, Boc - Met - D - Glu(OtBu)- His - OMe, Boc - Met - D - Glu(OtBu) - His- N 2 H 3 , Boc - Ala - D - Glu(OtBu) - His - N 2 H 3 , Boc - # - Ala - D - Glu(OtBu) - His - N 2 H 3 , desamino - Met - D - Glu(OtBu) - His - N 2 H 3 , Boc - Val - D - Glu(OtBu) - His - N 2 H 3 , Boc- (α - Me)Ala - D - Glu(OtBu) - His - N 2 H 3 , Boc - Gly - D - Glu(OtBu) - His - N 2 H 3 , ZGlu(OtBu) - D - His - OMe, Z - Glu(OtBu)- D - His - N 2 H 3 , H - Glu(OtBu) - D - His- OMe.2HCl, Boc - Met - Glu(OtBu) - D - His- OMe, Boc - Met - Glu(OtBu) - D - His - N 2 H 3 , Boc - # - Ala - Glu(OtBu) - D - His - OMe, Boc - # - Ala - Glu(OtBu) - D - His - N 2 H 3 , desamino - Met - Glu(OtBu) - D - His - N 2 H 3 , Boc - Gly - Glu(OtBu) - D - His - N 2 H 3 , Boc- (α - Me)Ala - Glu(OtBu) - D - His - N 2 H 3 , Boc- Val - Glu(OtBu) - D - His - N 2 H 3 , Boc - Ala- Glu(OtBu) - D - His - N 2 H 3 , Boc - Met - Gln- D - His - OMe, Boc - Met - Gln - D - His - N 2 H 3 , Z - Phe - D - Arg(NO 2 ) - OMe, Z - Phe - DArg(NO 2 ) - OH, H - Phe - D - Arg - OH.acetate, H - Phe - D - Arg - OMe.acetate, Z - Phe - Lys- (Boc) - OtBu, H - Phe - Lys(Boc) - OtBu, ZPhe - D - Lys(Boc) - OBzl, H - Phe - D - Lys(Boc)- OH, Z - Phe - Lys(Boc) - Trp - OH, H - Phe- Lys(Boc) - Trp - OH.HCl, Z - Phe - Lys(Boc)- Trp - NH 2 , Z - Phe - Lys(Boc) - Trp - N(CH 3 ) 2 , Z - Phe - Lys(Boc) - Trp - OC 11 H 23 , H - Phe- Lys(Boc) - Trp - NH 2 .HCl, H - Phe - Lys(Boc)- Trp - N(CH 3 ) 2 .HCl, H - Phe - Lys(Boc) - Trp- OC 11 H 23 .HCl, Boc - Arg(NO 2 ) - Trp - ONB, H - Arg(NO 2 ) - Trp - ONB, Z - Phe - Arg(NO 2 )- Trp - ONB, H - Phe - Arg - Trp - OH, ZPhe - Arg(NO 2 ) - Tra, H - Phe - Arg - Tra, Z - Phe - Lys(Boc) - Tra, H - Phe - Lys(Boc)- Tra, Z - Phe - Lys(Boc) - Phe - OMe, H - Phe- Lys(Boc) - Phe - OMe, H - Phe - Lys(Boc)- Phe - NH 2 , H - Phe - Lys(Boc) - Phe - OH, Z - D - Lys(Boc) - Phe - OtBu, H - D - Lys(Boc)- Phe - OtBu, Z - Phe - D - Lys(Boc) - Phe - OtBu, H - Phe - D - Lys(Boc) - Phe - OtBu, Z - Phe- Lys(Boc) - PPA, H - Phe - Lys(Boc) - PPA, HPhe - Lys(Boc) - L - Amf, H - Phe - Lys(Boc)- PEA, H - Phe - D - Lys(Boc) - HPEA, ZPhe - Lys(Boc) - N 2 H 3 , Z - Phe - Lys(Boc) - Phe- Gly - OBzl, H - Phe - Lys(Boc) - Phe - Gly - OH, Z - D - Lys(Boc) - Phe - Gly - OtBu, H - DLys(Boc) - Phe - Gly - OtBu, Z - Phe - D - Lys- (Boc) - Phe - Gly - OtBu and H - Phe - D - Lys- (Boc)-Phe-Gly-OtBu wherein Amf is N-(1- phenylisopropyl)amino, Tra is N-[#-(3-indolyl)- ethyl]amino, PEA is N-(2-phenylethyl)amino, PPA is N-(3-phenylpropyl)amino, HPEA is N - [2 - (p - hydroxyphenyl)ethyl]amino and ONB is p-nitrobenzyloxy. Pharmaceutical compositions having psychopharmacological activity comprise, as active ingredient, a peptide of the general formula above or a functional derivative thereof, together with a suitable carrier.